Abstract
Background
Cognitive impairment is a key feature of psychiatric illness, making cognition an
important tool for exploring of the genetics of illness risk. It remains unclear which
measures should be prioritized in pleiotropy-guided research. Here, we generate profiles
of genetic overlap between psychotic and affective disorders and cognitive measures
in Caucasian and Hispanic groups.
Methods
Data were from 4 samples of extended pedigrees (N = 3046). Coefficient of relationship analyses were used to estimate genetic overlap
between illness risk and cognitive ability. Results were meta-analyzed.
Results
Psychosis was characterized by cognitive impairments on all measures with a generalized
profile of genetic overlap. General cognitive ability shared greatest genetic overlap
with psychosis risk (average endophenotype ranking value [ERV] across samples from a random-effects meta-analysis = 0.32), followed by verbal memory
(ERV = 0.24), executive function (ERV = 0.22), and working memory (ERV = 0.21). For bipolar disorder, there was genetic overlap with processing speed (ERV = 0.05) and verbal memory (ERV = 0.11), but these were confined to select samples. Major depressive disorder was
characterized by enhanced working and face memory performance, as reflected in significant
genetic overlap in 2 samples.
Conclusions
There is substantial genetic overlap between risk for psychosis and a range of cognitive
abilities (including general intelligence). Most of these effects are largely stable
across of ascertainment strategy and ethnicity. Genetic overlap between affective
disorders and cognition, on the other hand, tends to be specific to ascertainment
strategy, ethnicity, and cognitive test battery.
Keywords
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Article info
Publication history
Published online: March 17, 2021
Accepted:
March 10,
2021
Received in revised form:
January 8,
2021
Received:
September 8,
2020
Identification
Copyright
© 2021 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
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Access this article on ScienceDirectLinked Article
- Cognitive Endophenotypes: Powerful Tools for Modern Neuropsychiatric Genomics ResearchBiological PsychiatryVol. 90Issue 6
- PreviewProfound cognitive deficits are a common feature of schizophrenia, and substantial impairments are also seen in bipolar disorder (BD) and major depressive disorder, albeit less frequently recognized. These impairments span the range of fluid intelligence functions, with the most severe tending to be in processing speed, working and episodic memory, and executive functioning, and can affect crystallized intelligence by reducing educational attainment. Cognitive deficits are highly correlated with impairments in the ability to perform everyday tasks, called functional capacity, affecting independence in residence, social capability, and employment, and thus directly contribute to the disability associated with these disorders.
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